Lysine

Lysine
IUPAC name Lysine
Other names 2,6-diaminohexanoic acid
Identifiers
CAS number	70-54-2,  L: [56-87-1] D: [923-27-3]
PubChem	866
ChemSpider	843
IUPHAR ligand	724
SMILES C(CCN)CC(C(=O)O)N
Properties
Molecular formula	C6H14N2O2
Molar mass	146.19 g mol−1
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Lysine (abbreviated as Lys or K)^[1] is an α-amino acid with the chemical formula HO₂CCH(NH₂)(CH₂)₄NH₂. This amino acid is an essential amino acid, which means that humans cannot synthesize it. Its codons are AAA and AAG.

Lysine is a base, as are arginine and histidine. The ε-amino group often participates in hydrogen bonding and as a general base in catalysis. Common posttranslational modifications include methylation of the ε-amino group, giving methyl-, dimethyl-, and trimethyllysine. The latter occurs in calmodulin. Other posttranslational modifications at lysine residues include acetylation and ubiquitination. Collagen contains hydroxylysine which is derived from lysine by lysyl hydroxylase. O-Glycosylation of lysine residues in the endoplasmic reticulum or Golgi apparatus is used to mark certain proteins for secretion from the cell.

Biosynthesis

As an essential amino acid, lysine is not synthesized in animals, hence it must be ingested as lysine or lysine-containing proteins. In plants and bacteria, it is synthesized from aspartic acid (aspartate):^[2]

• L-aspertate is first converted to L-aspartyl-4-phosphate by Aspartokinase (or Aspartate kinase). ATP is needed as an energy source for this step.
• β-aspartate semialdehyde dehydrogenase converts this into β-aspartyl-4-semialdehyde (or β-aspartate-4-semialdehyde). Energy from NADPH is used in this conversion.
• Dihydrodipicolinate synthase adds a Pyruvate group to the β-aspartyl-4-semialdehyde, and two water molecules are removed. This causes cyclization and gives rise to 2,3-dihydrodipicolinate.
• This product is reduced to 2,3,4,5-tetrahydrodipicolinate (or Δ¹-piperidine-2,6-dicarboxylate, in the figure: (S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylate) by Dihydrodipicolinate reductase. This reaction consumes a NADPH molecule.
• Tetrahydrodipicolinate N-acetyltransferase opens this ring and gives rise to N-succinyl-L-2-amino-6-oxoheptanedionate (or N-acyl-2-amino-6-oxopimelate). Two water molecules and one Acyl-CoA (Succinyl-CoA) enzyme are used in this reaction.
• N-succinyl-L-2-amino-6-oxoheptanedionate is converted into N-succinyl-LL-2,6-diaminoheptanedionate (N-acyl-2,6-diaminopimelate). This reaction is catalyzed by the enzyme Succinyl diaminopimelate aminotransferase. A Glutaric acid molecule is used in this reaction and an Oxoacid is produced as a byproduct.
• N-succinyl-LL-2,6-diaminoheptanedionate (N-acyl-2,6-diaminopimelate)is converted into LL-2,6-diaminoheptanedionate (L,L-2,6-diaminopimelate) by Succinyl diaminopimelate desuccinylase (Acyldiaminopimelate deacylase). A water molecule is consumed in this reaction and a succinate is produced a byproduct.
• LL-2,6-diaminoheptanedionate is converted by Diaminopimelate epimerase into meso-2,6-diamino-heptanedionate (meso-2,6-diaminopimelate).
• Finally meso-2,6-diamino-heptanedionate is converted into L-lysine by Diaminopimelate decarboxylase.

Enzymes involved in this biosynthesis include:^[3]

1. Aspartokinase
2. β-aspartate semialdehyde dehydrogenase
3. Dihydropicolinate synthase
4. Δ¹-piperidine-2,6-dicarboxylate dehydrogenase
5. N-succinyl-2-amino-6ketopimelate synthase
6. Succinyl diaminopimelate aminotransferase
7. Succinyl diaminopimelate desuccinylase
8. Diaminopimelate epimerase
9. Diaminopimelate decarboxylase.

Metabolism

Lysine is metabolised in mammals to give acetyl-CoA, via an initial transamination with α-ketoglutarate. The bacterial degradation of lysine yields cadaverine by decarboxylation.

Allysine is a derivative of lysine, used in the production of elastin and collagen. It is produced by the actions of the enzyme lysyl oxidase on lysine in the extracellular matrix and is essential in the crosslink formation that stabilizes collagen and elastin.

Synthesis

Synthetic, racemic lysine has long been known.^[4] A practical synthesis starts from caprolactam.^[5] Industrially, L-lysine is usually manufactured by a fermentation process using Corynebacterium glutamicum; production exceeds 600,000 tons a year.^[6]

Dietary sources

The human nutritional requirement is 1–1.5 g daily. It is the limiting amino acid (the essential amino acid found in the smallest quantity in the particular foodstuff) in all cereal grains, but is plentiful in all pulses (legumes). Foods that contain significant amounts of lysine include:

• Red Meat (14,200–15,000 ppm)
• Eggs
• Buffalo Gourd (10,130–33,000 ppm) in seed
• Watercress (1,340–26,800 ppm) in herb.
• Soybean (24,290–26,560 ppm) in seed.
• Carob, Locust Bean, St.John's-Bread (26,320 ppm) in seed;
• Common Bean (Black Bean, Dwarf Bean, Field Bean, Flageolet Bean, French Bean, Garden Bean, Green Bean, Haricot, Haricot Bean, Haricot Vert, Kidney Bean, Navy Bean, Pop Bean, Popping Bean, Snap Bean, String Bean, Wax Bean) (2,390–25,700 ppm) in sprout seedling;
• Ben Nut, Benzolive Tree, Jacinto (Sp.), Moringa (aka Drumstick Tree, Horseradish Tree, Ben Oil Tree), West Indian Ben (5,370–25,165 ppm) in shoot.
• Lentil (7,120–23,735 ppm) in sprout seedling.
• Asparagus Pea, Winged Bean (aka Goa Bean) (21,360–23,304 ppm) in seed.
• Fat Hen (3,540–22,550 ppm) in seed.
• White Lupin (19,330–21,585 ppm) in seed.
• Black Caraway, Black Cumin, Fennel-Flower, Nutmeg-Flower, Roman Coriander (16,200–20,700 ppm) in seed.
• Pea (3,170–14,995 ppm) in seed.
• Spinach (1,740–20,664 ppm).
• Amaranth, Quinoa
• Buckwheat
• Mesquite.

Good sources of lysine are foods rich in protein including meat (specifically red meat, lamb, pork, and poultry), cheese (particularly Parmesan), certain fish (such as cod and sardines), and eggs.^[7]

Properties

L-Lysine is a necessary building block for all protein in the body. L-Lysine plays a major role in calcium absorption; building muscle protein; recovering from surgery or sports injuries; and the body's production of hormones, enzymes, and antibodies.

Modifications

Lysine can be modified through acetylation, methylation, ubiquitination, sumoylation, neddylation, biotinylation and carboxylation which tends to modify the function of the protein of which the modified lysine residue(s) are a part.^[8]

Clinical significance

It has been suggested that lysine may be beneficial for those with herpes simplex infections.^[9] However, more research is needed to fully substantiate this claim. For more information, refer to Herpes simplex - Lysine.

There are Lysine conjugates that show promise in the treatment of cancer, by causing cancerous cells to destroy themselves when the drug is combined with the use of phototherapy, while leaving non-cancerous cells unharmed.^[10]

While chemically insignificant to lysine itself, it is worth noting that lysine is attached to dextroamphetamine to form the prodrug lisdexamfetamine (Vyvanse). In the gastrointestinal tract, the lysine molecule is cleaved from the dextroamphetamine, thereby making oral administration necessary.

In popular culture

The 1993 film Jurassic Park, which is based on the 1990 Michael Crichton novel Jurassic Park, features dinosaurs that were genetically altered so they could not produce lysine.^[11] This was known as the "lysine contingency," and was supposed to prevent the cloned dinosaurs from surviving outside the park, forcing them to be dependent on lysine supplements provided by the park's veterinary staff. Most vertebrates cannot produce lysine by default (it is an essential amino acid).

In 1996, lysine became the focus of the largest successful conviction of a price fixing case in United States history. The Archer Daniels Midland Company paid a fine of US$100 million, and three of its executives were convicted and served prison time. Also found guilty in the price fixing case were two Japanese firms (Ajinomoto, Kyowa Hakko) and a South Korean firm (Sewon).^[12] Secret video recordings of the conspirators fixing lysine's price can be found online or by requesting the video from the U.S. Department of Justice, Antitrust Division. This case served as the basis of the movie The Informant!, and a book of the same title.^[13]

Linus Pauling believed people with existing angina and atherosclerotic plaque can benefit from vitamin C and the amino acid lysine. Pauling filmed a video lecture in which he recommended that heart patients take between 2,000 and 6,000 mg of lysine daily with their vitamin C (more if serum Lp(a) is elevated).

Musician Max Tundra, (real name Ben Jacobs), wrote a song about Lysine on his 2002 album "Mastered by Guy at the Exchange." The song details the importance of lysine and which foods it can be most readily found in.

Lysine is the favourite amino acid of the main character Sheldon in the TV series "The Big Bang Theory".

See also

• Acetyllysine
• Lysine price-fixing conspiracy
• Deamination
• Saccharopine

References

Sources

• Much of the information in this article has been translated from German Wikipedia.
• Lide, D. R., ed. (2002), CRC Handbook of Chemistry and Physics (83rd ed.), Boca Raton, FL: CRC Press, ISBN 0-8493-0483-0